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. 2020 Dec;267(12):3643-3649.
doi: 10.1007/s00415-020-10059-3. Epub 2020 Jul 12.

Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion

Grace McMacken  1 , Hanns Lochmüller  2   3   4 , Boglarka Bansagi  5 , Angela Pyle  5 , Angela Lochmüller  6 , Patrick F Chinnery  7   8 , Steve Laurie  3 , Sergi Beltran  3 , Leslie Matalonga  3 , Rita Horvath  9   10
Affiliations

Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion

Grace McMacken et al. J Neurol. 2020 Dec.

Abstract

Background: Behr syndrome is a clinically distinct, but genetically heterogeneous disorder characterized by optic atrophy, progressive spastic paraparesis, and motor neuropathy often associated with ataxia. The molecular diagnosis is based on gene panel testing or whole-exome/genome sequencing.

Methods: Here, we report the clinical presentation of two siblings with a novel genetic form of Behr syndrome. We performed whole-exome sequencing in the two patients and their mother.

Results: Both patients had a childhood-onset, slowly progressive disease resembling Behr syndrome, starting with visual impairment, followed by progressive spasticity, weakness, and atrophy of the lower legs and ataxia. They also developed scoliosis, leading to respiratory problems. In their late 30's, both siblings developed a hypertrophic cardiomyopathy and died of sudden cardiac death at age 43 and 40, respectively. Whole-exome sequencing identified the novel homozygous c.627_629del; p.(Gly210del) deletion in UCHL1.

Conclusions: The presentation of our patients raises the possibility that hypertrophic cardiomyopathy may be an additional feature of the clinical syndrome associated with UCHL1 mutations, and highlights the importance of cardiac follow-up and treatment in neurodegenerative disease associated with UCHL1 mutations.

Keywords: Ataxia; Behr syndrome; Hereditary spastic paraplegia; Neurogenetics; Whole exome sequencing.

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Conflict of interest statement

The authors have no conflict of interest.

Figures

Fig. 1
Fig. 1
a P1 aged 40 years (left) and P2 aged 38 years. Both patients have characteristic facial features low-set ears and, and presented with distal upper and lower limb wasting and equinovarus deformity due to peripheral neuropathy and spastic paraparesis. b Axial T2 FLAIR MR images of P1 (top panels) and P2 (bottom panels). MRI brain in P1 aged 41 years showed mild global atrophy. MRI brain in P2 aged 34 demonstrated no significant abnormality apart from mild increased T2 signal in the peritrigonal white matter bilaterally
Fig. 2
Fig. 2
a Pathogenic mutations identified in UCLH1. b Consanguinity analysis through run of homozygosity (ROH) > 1 Mbp detection in autosomal chromosomes. c Conservation of the amino acid affected by the c.627_629del; p.(Gly210del) UCHL1 mutation
See this image and copyright information in PMC

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